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Yorodumi- PDB-3cdb: Thermodynamic and structure guided design of statin hmg-coa reduc... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3cdb | ||||||
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Title | Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors | ||||||
Components | 3-hydroxy-3-methylglutaryl-coenzyme A reductase | ||||||
Keywords | OXIDOREDUCTASE / CHOLESTEROL BIOSYNTHESIS / HMG-COA / NADPH / STATIN / Alternative splicing / Endoplasmic reticulum / Glycoprotein / Lipid synthesis / Membrane / Peroxisome / Polymorphism / Steroid biosynthesis / Transmembrane | ||||||
Function / homology | Function and homology information hydroxymethylglutaryl-CoA reductase (NADPH) / hydroxymethylglutaryl-CoA reductase (NADPH) activity / sterol biosynthetic process / GTPase regulator activity / coenzyme A binding / negative regulation of amyloid-beta clearance / Cholesterol biosynthesis / EGR2 and SOX10-mediated initiation of Schwann cell myelination / coenzyme A metabolic process / isoprenoid biosynthetic process ...hydroxymethylglutaryl-CoA reductase (NADPH) / hydroxymethylglutaryl-CoA reductase (NADPH) activity / sterol biosynthetic process / GTPase regulator activity / coenzyme A binding / negative regulation of amyloid-beta clearance / Cholesterol biosynthesis / EGR2 and SOX10-mediated initiation of Schwann cell myelination / coenzyme A metabolic process / isoprenoid biosynthetic process / peroxisomal membrane / cholesterol biosynthetic process / negative regulation of protein secretion / regulation of ERK1 and ERK2 cascade / NADPH binding / Activation of gene expression by SREBF (SREBP) / negative regulation of protein catabolic process / long-term synaptic potentiation / PPARA activates gene expression / visual learning / endoplasmic reticulum membrane / endoplasmic reticulum Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.3 Å | ||||||
Authors | Pavlovsky, A. / Sarver, R.W. / Harris, M.S. / Finzel, B.C. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2008 Title: Thermodynamic and structure guided design of statin based inhibitors of 3-hydroxy-3-methylglutaryl coenzyme a reductase. Authors: Sarver, R.W. / Bills, E. / Bolton, G. / Bratton, L.D. / Caspers, N.L. / Dunbar, J.B. / Harris, M.S. / Hutchings, R.H. / Kennedy, R.M. / Larsen, S.D. / Pavlovsky, A. / Pfefferkorn, J.A. / Bainbridge, G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3cdb.cif.gz | 323.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3cdb.ent.gz | 262.5 KB | Display | PDB format |
PDBx/mmJSON format | 3cdb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3cdb_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 3cdb_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 3cdb_validation.xml.gz | 64.5 KB | Display | |
Data in CIF | 3cdb_validation.cif.gz | 89.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cd/3cdb ftp://data.pdbj.org/pub/pdb/validation_reports/cd/3cdb | HTTPS FTP |
-Related structure data
Related structure data | 3cctC 3ccwC 3cczC 3cd0C 3cd5C 3cd7C 3cdaC C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 47479.551 Da / Num. of mol.: 4 / Fragment: CATALYTIC DOMAIN (RESIDUES 441-875) / Mutation: M485I Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HMGCR / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 STAR References: UniProt: P04035, hydroxymethylglutaryl-CoA reductase (NADPH) #2: Chemical | ChemComp-9HI / ( #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.24 Å3/Da / Density % sol: 45.1 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8 Details: protein 15-20 mg/ml, Ligand (saturated),PEG 4000, MgCl2 0.2M, Tris-HCL pH8 0.1M, 7-10 days, pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-BM / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MAR CCD 165 mm / Detector: CCD / Date: Jul 10, 2003 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Redundancy: 3.1 % / Av σ(I) over netI: 8.7 / Number: 211701 / Rmerge(I) obs: 0.063 / Χ2: 0.86 / D res high: 2.3 Å / D res low: 50 Å / Num. obs: 68943 / % possible obs: 92.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diffraction reflection shell |
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Reflection | Resolution: 2.3→50 Å / Num. obs: 68943 / % possible obs: 92.8 % / Redundancy: 3.1 % / Rmerge(I) obs: 0.063 / Χ2: 0.858 / Net I/σ(I): 8.7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→50 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.915 / SU B: 8.074 / SU ML: 0.189 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.491 / ESU R Free: 0.257 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 32.583 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→50 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.3→2.36 Å / Total num. of bins used: 20
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